Publications by authors named "Daniel Salas-Escabillas"
Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown.
View Article and Find Full Text PDFPurpose: Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard of care treatments and have significantly worse overall survival (OS) compared to patients with classical subtype enriched tumors. It is important to develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner.
Experimental Design: We compiled a single cell RNA sequencing (scRNAseq) atlas of the human pancreas with 229 patient samples, aggregated from publicly available raw data.
Article Synopsis
- Cellular plasticity in pancreatic ductal adenocarcinoma (PDAC) involves the transformation of normal cells into precancerous lesions and more aggressive cancer subtypes, affecting treatment responses.
- Researchers found that the transcription factor Pdx1 helps maintain normal acinar cell differentiation and suppresses a gastric cell identity linked to PDAC development in both mice and humans.
- The receptor tyrosine kinase Ror2 was identified as a marker for gastric metaplasia in pancreatic tumors, and its removal in mouse models led to a shift toward a gastric pit cell identity, which affected cancer progression and treatment resistance.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDA) starts with acinar cells turning into metaplastic duct cells, which are important in the development of cancer.
- Tuft cells, which emerge during this process, initially help suppress tumor growth but their role during cancer progression is unclear.
- Research using a special lineage tracing model shows that in advanced PDA, metaplastic tuft cells transform into neural-like progenitor cells, indicating a shift that correlates with worse outcomes for patients.
Article Synopsis
- Cellular plasticity in pancreatic ductal adenocarcinoma (PDAC) involves the transformation of normal cells into precancerous stages and aggressive carcinoma types, impacting treatment responses.* -
- The transcription factor Pdx1 plays a role in maintaining normal acinar cell differentiation and suppressing a gastric cell identity, which is linked to disease progression in PDAC.* -
- The receptor tyrosine kinase Ror2 is identified as a marker for gastric metaplasia in the pancreas, and its activity influences cellular identity, promoting resistance to certain cancer treatments while creating vulnerabilities to others.*
An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it is well appreciated that macrophages are immunosuppressive and contribute to the poor response to immunotherapy; however, the mechanisms of immune suppression are complex and not fully understood. Immunosuppressive macrophages are classically defined by the expression of the enzyme Arginase 1 (ARG1), which we demonstrated is potently expressed in pancreatic tumor-associated macrophages from both human patients and mouse models.
View Article and Find Full Text PDFProper Hedgehog (HH) signaling is essential for embryonic development, while aberrant HH signaling drives pediatric and adult cancers. HH signaling is frequently dysregulated in pancreatic cancer, yet its role remains controversial, with both tumor-promoting and tumor-restraining functions reported. Notably, the GLI family of HH transcription factors (GLI1, GLI2, GLI3), remain largely unexplored in pancreatic cancer.
View Article and Find Full Text PDFThe Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice.
Cell Mol Gastroenterol Hepatol
December 2021
Article Synopsis
- The study investigates how chemosensory signaling, specifically through the G-protein GNAT3 in metaplastic tuft cells, influences the initiation and progression of pancreatic ductal adenocarcinoma (PDA).
- Researchers created genetically modified mice to observe the effects of disrupting GNAT3 on tumor-promoting cytokine secretion and the role of myeloid-derived suppressor cells (MDSCs) during PDA progression.
- Results showed that the absence of GNAT3 increased cytokine levels and MDSC populations, leading to more aggressive cancer development and faster progression to metastatic carcinoma.